SLC19A1 p.Thr404=
c.1212G>A · rs138417012 · VCV2077276
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.067%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.041 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP -12 | GERP -3.5 |
| Overall | ||
| CADD | 0.071 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.067%
European (non-Finnish) · 790/1,179,956 alleles
Filtering AF
0.063%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0615%
Overall
0.0543%
877/1,613,666 alleles · ultra-rare
exomes 827/1,461,304 · genomes 50/152,362 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.067% | 1,494 |
| Remaining individualsnot grpmax-eligible | 0.0592% | 1,689 |
| South Asian | 0.0274% | 3,643 |
| East Asian | 0.0156% | 6,412 |
| Admixed American | 0.015% | 6,670 |
| African / African-American | 0.012% | 8,341 |
Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.
Variant & gene context
- Gene
- SLC19A1
- Protein
- p.Thr404=
- Coding
- c.1212G>A
- MANE Select
- NM_194255
- dbSNP
- rs138417012
- Type
- single nucleotide variant
- Location
- chr21:45525898 (GRCh38)
- Gene constraint
- LOEUF 1.585 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 73.30 · 19 PDB
- Residue 404
- an α-helix
Similar variants
- SLC19A1 p.Thr404Met Uncertain significance ★ ⚠ same residue
- COL18A1 p.Arg1081Ter Pathogenic/Likely pathogenic ★★ same type
- COL18A1 p.Arg915Ter Pathogenic/Likely pathogenic ★★ same type
- RFC1 p.Arg383Ter Pathogenic/Likely pathogenic ★★ same type
- COL18A1 c.*30G>A Uncertain significance ★★ same type
- COL18A1 p.Ala1089Thr Uncertain significance ★★ ⚠ same type
- COL18A1 p.Ala1254Val Uncertain significance ★★ ⚠ same type
- COL18A1 p.Arg1081Gln Uncertain significance ★★ ⚠ same type
Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →
Cite Sugi Variant
Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/slc19a1-p-thr404 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown